rs10483452

Positions:

• chr14-35087292-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017917.4(PPP2R3C):​c.1173+659T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,256 control chromosomes in the GnomAD database, including 3,956 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3956 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP2R3C NM_017917.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

Genes affected

PPP2R3C (HGNC:17485): (protein phosphatase 2 regulatory subunit B''gamma) This gene encodes a regulatory subunit of the serine/threonine phosphatase, protein phosphatase 2. This protein is localized to both nuclear and cytoplasmic regions depending on cell cycle phase. Homozygous conditional knockout mice for this gene exhibit reduced numbers and impaired proliferation of immune system B cells. This protein may regulate the expression of the P-glycoprotein ATP-binding cassette transporter through its phosphatase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

(HGNC:):

FAM177A1 (HGNC:19829): (family with sequence similarity 177 member A1) This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R3C	NM_017917.4	c.1173+659T>G		intron_variant		ENST00000261475.10	NP_060387.2
LOC101927178	NR_110415.1	n.479+5733A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R3C	ENST00000261475.10	c.1173+659T>G		intron_variant		1	NM_017917.4	ENSP00000261475	P1
	ENST00000624600.1	n.1258A>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31615 AN: 152138 Hom.: 3960 Cov.: 33

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0698

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.234

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.208 AC: 31614 AN: 152256 Hom.: 3956 Cov.: 33 AF XY: 0.202 AC XY: 15074 AN XY: 74444

Gnomad4 AFR AF: 0.0815

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.0697

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.232

Alfa AF: 0.255 Hom.: 2551

Bravo AF: 0.202

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.0
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10483452; hg19: chr14-35556498;